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The Molecular Perspective: Bcl-2 and ApoptosisCorrespondence: David S. Goodsell, Ph.D., Associate Professor, The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-2839; Fax: 858-784-2860; e-mail: goodsell{at}scripps.edu Website: http://www.scripps.edu/pub/goodsell
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Animals enforce a strict capital punishment on their cells. If any cell steps out of line, it is cleanly and promptly destroyed through the process of apoptosis. Candidates for apoptosis include cells that may be a danger to the organism, such as cells with damaged DNA or cells growing at improper rates. Apoptosis, however, is not restricted to rogue cells. It is also widely applied to normal cells that have simply become obsolete as organisms grow and develop. Of course, there must be checks and balances on this powerful system. In cells, apoptosis is controlled through a tribunal of proteins, together known as the Bcl-2 family of proteins. Together, they weigh the pros and cons of cell death at any given time. Some of these proteins are pro-survival, arguing that the cell is healthy and useful. They normally dominate, and the cell continues living and performing its daily duties. Other proteins are pro-apoptotic, arguing for cell death. If they come to dominate, the mechanisms of apoptosis are activated and the cell destroys itself. Cancer cells, in order to survive, must fool this watchdog system, continuing growth even when given death signals. In some cases, a mutation somewhere in the Bcl-2 system allows cancer cells to circumvent apoptosis. For instance, most follicular B-cell lymphomas contain a chromosomal translocation that moves the gene for Bcl-2 from its normal location to a position within the genes for immunoglobulins. In this new location, higher quantities of Bcl-2 are produced. Since Bcl-2 is a potent pro-survival advocate, it then shields the cancer cells from apoptotic instructions.
Over a dozen Bcl-2 family proteins have been discovered. About half, such as the BID protein shown in Figure 1
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